Amelioration and elimination of fever are important therapeutic endpoints in the treatment of a wide variety of undesirable physiological conditions. The present invention provides a method whereby fever (i.e., elevated body temperature) is reduced or eliminated in humans by systemic administration of certain hypothermic prostaglandins. In particular, .omega.-aryl-PGF.sub..alpha. -type compounds are disclosed herein as hypothermic prostaglandins capable of reducing or eliminating fever in a dose-response manner.
Human thermo-regulatory function is centered in the hypothalamus and both hypothermic (temperature lowering) and hyperthermic (temperature raising) substances are known to interplay in the control of body temperature. See, for example, Proceedings of the Royal Society of London, Bulletin 191:199-229 (1975) and Karim, S.S.M., Ed., Prostaglandin Physiological Pharmacological and Pathological Aspects, MTP Press, Ltd., Lancaster, U.K. (1975) pages 13-17, for a discussion of the interplay of certain monoamines (i.e., 5-hydroxytryptamine and norepinephrine) and acetylcholine.
The above references not only describe pyrogen induction of fever and idiopathic fever, but further describe "prostaglandin fever," characteristically induced by administration of prostaglandin E.sub.1 and related compounds. See Veale, et al., Pharmacology, Biochemistry and Behavior, 4:143-150 (1976).
Further evidence for the pyretic effects of prostaglandin E.sub.1 are suggested by the characteristic of known antipyretic agents as further being inhibitors of prostaglandin synthetase. See, for example, the references cited in Karim, indicating that pyrogen-induced fever is susceptible to treatment with antipyretic prostaglandin synthetase inhibitors, while fever induced by exogenous prostaglandin administration is not.